{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T07:44:29Z","timestamp":1781163869769,"version":"3.54.1"},"reference-count":10,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,4,20]],"date-time":"2023-04-20T00:00:00Z","timestamp":1681948800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["NIHR03DE030550"],"award-info":[{"award-number":["NIHR03DE030550"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["NIHK23DE029811"],"award-info":[{"award-number":["NIHK23DE029811"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R211R21CA267152"],"award-info":[{"award-number":["R211R21CA267152"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Head &amp; Neck"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Human papillomavirus\u2010associated head and neck squamous cell carcinoma (HPV\u2009+\u2009HNSCC) occurs in the oropharynx (HPV\u2009+\u2009OPSCC), sinonasal cavity (HPV\u2009+\u2009SNSCC), and nasopharynx (HPV\u2009+\u2009NPC). Circulating tumor HPV DNA (ctHPVDNA) is an accurate tool for diagnosis, treatment monitoring, and recurrence detection. An emerging challenge with ctHPVDNA is that ~7.4% of HPV\u2009+\u2009HNSCC patients develop synchronous or metachronous HPV+ primaries, which could confound ctHPVDNA monitoring.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We describe a 65\u2010year\u2010old patient with T2N1M0 HPV16\u2009+\u2009OPSCC and a 55\u2010year\u2010old patient with T2N2M0 HPV16\u2009+\u2009OPSCC. Both patients were enrolled in our prospective observational ctHPVDNA study with longitudinal blood collections throughout treatment. Both patients developed multiple HPV+ primaries.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Detailed discussion of the patients' treatment courses, the subsequent diagnoses of their second HPV+ primaries, and their ctHPVDNA monitoring is presented.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>As ctHPVDNA use becomes more prevalent, it is important to recognize that an increase in ctHPVDNA can come not only from the primary tumor or metastatic clones, but also from synchronous or metachronous second primaries.<\/jats:p><\/jats:sec>","DOI":"10.1002\/hed.27378","type":"journal-article","created":{"date-parts":[[2023,4,21]],"date-time":"2023-04-21T02:37:02Z","timestamp":1682044622000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Double trouble: Synchronous and metachronous primaries confound <scp>ctHPVDNA<\/scp> monitoring"],"prefix":"10.1002","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0935-7861","authenticated-orcid":false,"given":"Saskia","family":"Naegele","sequence":"first","affiliation":[{"name":"Department of Otolaryngology \u2013 Head and Neck Surgery Massachusetts Eye and Ear  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vasileios","family":"Efthymiou","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology \u2013 Head and Neck Surgery Massachusetts Eye and Ear  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shun","family":"Hirayama","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian Y.","family":"Zhao","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dipon","family":"Das","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology \u2013 Head and Neck Surgery Massachusetts Eye and Ear  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annie W.","family":"Chan","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts USA"},{"name":"Department of Radiation Oncology Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6588-6549","authenticated-orcid":false,"given":"Jeremy D.","family":"Richmon","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology \u2013 Head and Neck Surgery Massachusetts Eye and Ear  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A. John","family":"Iafrate","sequence":"additional","affiliation":[{"name":"Harvard Medical School  Boston Massachusetts USA"},{"name":"Massachusetts General Hospital Cancer Center  Boston Massachusetts USA"},{"name":"Department of Pathology Massachusetts General Hospital  Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Faden","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology \u2013 Head and Neck Surgery Massachusetts Eye and Ear  Boston Massachusetts USA"},{"name":"Harvard Medical School  Boston Massachusetts USA"},{"name":"Broad Institute of MIT and Harvard  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,4,20]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13010045"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.34266"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/hed.26976"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-3151"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.34109"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-21-2338"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2019.104475"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.oraloncology.2021.105212"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgaa111"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2022.55971"}],"container-title":["Head &amp; Neck"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/hed.27378","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T14:09:58Z","timestamp":1692713398000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/hed.27378"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,20]]},"references-count":10,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1002\/hed.27378"],"URL":"https:\/\/doi.org\/10.1002\/hed.27378","archive":["Portico"],"relation":{},"ISSN":["1043-3074","1097-0347"],"issn-type":[{"value":"1043-3074","type":"print"},{"value":"1097-0347","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,20]]},"assertion":[{"value":"2023-03-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-04-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}